Gastroenterology · 2002
Mechanisms of diarrhea in collagenous colitis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Bürgel Natalie, Bojarski Christian, Mankertz Joachim, Zeitz Martin, Fromm Michael, Schulzke Jörg-Dieter
Аннотация
BACKGROUND & AIMS: Collagenous colitis is an inflammatory disease of unknown etiology with diarrhea as the leading symptom. The aim of this study was to examine the pathogenic mechanisms of this disease.
METHODS: Biopsy specimens of the sigmoid colon were obtained endoscopically. Short-circuit current and (22)Na and (36)Cl fluxes were measured in miniaturized Ussing chambers. Alternating current impedance analysis discriminated epithelial from subepithelial resistance. Tight junction proteins occludin and claudin 1-5 were characterized in membrane fractions by Western blotting. Apoptotic ratio was determined by DAPI and TUNEL staining.
RESULTS: In collagenous colitis, net Na(+) flux decreased from 8.8 +/- 1.8 to 0.2 +/- 1.5 and net Cl(-) flux from 11.2 +/- 3.0 to -3.0 +/- 2.7 micromol x h(-1) x cm(-2), indicating a pronounced decrease in NaCl absorption. The fact that short-circuit current increased from 1.5 +/- 0.4 to 3.9 +/- 0.8 micromol x h(-1) x cm(-2), together with the negative net Cl(-) flux, points to activation of active electrogenic chloride secretion. Subepithelial resistance increased from 7 +/- 1 to 18 +/- 2 Omega x cm(2) due to subepithelial collagenous bands of 48 +/- 8-microm thickness. Epithelial resistance was diminished from 44 +/- 3 to 29 +/- 2 Omega x cm(2), and this was accompanied by a decrease in occludin and claudin-4 expression. Neither mucosal surface area nor apoptotic ratio was altered in collagenous colitis.
CONCLUSIONS: Reduced net Na(+) and Cl(-) absorption is the predominant diarrheal mechanism in collagenous colitis, accompanied by a secretory component of active electrogenic chloride secretion. The subepithelial collagenous band as a significant diffusion barrier is a cofactor. Down-regulation of tight junction molecules but not epithelial apoptoses is a structural correlate of barrier dysfunction contributing to diarrhea by a leak flux mechanism.
METHODS: Biopsy specimens of the sigmoid colon were obtained endoscopically. Short-circuit current and (22)Na and (36)Cl fluxes were measured in miniaturized Ussing chambers. Alternating current impedance analysis discriminated epithelial from subepithelial resistance. Tight junction proteins occludin and claudin 1-5 were characterized in membrane fractions by Western blotting. Apoptotic ratio was determined by DAPI and TUNEL staining.
RESULTS: In collagenous colitis, net Na(+) flux decreased from 8.8 +/- 1.8 to 0.2 +/- 1.5 and net Cl(-) flux from 11.2 +/- 3.0 to -3.0 +/- 2.7 micromol x h(-1) x cm(-2), indicating a pronounced decrease in NaCl absorption. The fact that short-circuit current increased from 1.5 +/- 0.4 to 3.9 +/- 0.8 micromol x h(-1) x cm(-2), together with the negative net Cl(-) flux, points to activation of active electrogenic chloride secretion. Subepithelial resistance increased from 7 +/- 1 to 18 +/- 2 Omega x cm(2) due to subepithelial collagenous bands of 48 +/- 8-microm thickness. Epithelial resistance was diminished from 44 +/- 3 to 29 +/- 2 Omega x cm(2), and this was accompanied by a decrease in occludin and claudin-4 expression. Neither mucosal surface area nor apoptotic ratio was altered in collagenous colitis.
CONCLUSIONS: Reduced net Na(+) and Cl(-) absorption is the predominant diarrheal mechanism in collagenous colitis, accompanied by a secretory component of active electrogenic chloride secretion. The subepithelial collagenous band as a significant diffusion barrier is a cofactor. Down-regulation of tight junction molecules but not epithelial apoptoses is a structural correlate of barrier dysfunction contributing to diarrhea by a leak flux mechanism.